Inhibition of the small GTPase RhoA or its downstream target Rho-associated coiled kinase (ROCK) has been shown to promote axon regeneration and to improve functional recovery followingspinalcordinjury (SCI) in the adult rat. RhoA has also been implicated in delayed secondary injury pathophysiology, such as free radical formation and loss of endothelial integrity leading to edema formation. In the present report, we have analyzed the effect of the central nervous system (CNS) permissive, putatively neuroprotective, anti-inflammatory cyclooxygenase-1/-2 (COX-1/-2) inhibitor indomethacin in CNS effective dosage (2 mg/kg/day) on lesionalRhoA expression followingsubacutespinalcordinjury. In control rats receiving vehicle alone, RhoA+ cells accumulate at the lesion site (Th8). At day 3 following SCI, the RhoA+ cellular composition is composed prevailingly of microglia/macrophages and polymononuclear granulocytes, but few reactive astrocytes. In contrast, in the verum group, lesionalnumbers of RhoA cells were reduced by indomethacin treatment by more than 60% (P < 0.0001). Inflammation-dependent RhoA expression accessible by cyclooxygenase inhibition proposes an immune-related mechanism. Our results identify COX blockers as candidates for a safe, synergistic, adjuvant treatment option in combination with cell-specific approaches to Rho inactivation, effectively minimizing the pool of RhoA+ cells at the lesion site following SCI.